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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4170-4177. Prepublished online as a Blood First Edition Paper on July 10, 2008; DOI 10.1182/blood-2008-04-149161. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-04-149161v1 blood-2008-04-149161v2 112/10/4170    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Beers, S. A. Articles by Glennie, M. J. Search for Related Content PubMed PubMed Citation Articles by Beers, S. A. Articles by Glennie, M. J. Related Collections Immunobiology Neoplasia Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Type II (tositumomab) anti-CD20 monoclonal antibody out performs type I (rituximab-like) reagents in B-cell depletion regardless of complement activation Stephen A. Beers1, Claude H. T. Chan1, Sonya James1, Ruth R. French1, Kathrine E. Attfield1, Claire M. Brennan1, Anupama Ahuja2, Mark J. Shlomchik2, Mark S. Cragg1,*, and Martin J. Glennie1,* 1 Tenovus Laboratory, Cancer Sciences Division, Southampton University School of Medicine, General Hospital, Southampton, United Kingdom; and 2 Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT Anti-CD20 monoclonal antibodies (mAbs) are classified into type I (rituximab-like) or type II (tositumomab-like) based on their ability to redistribute CD20 molecules in the plasma membrane and activate various effector functions. To compare type I and II mAbs directly in vivo and maximize Fc effector function, we selected and engineered mAbs with the same mouse IgG2a isotype and assessed their B-cell depleting activity in human CD20 transgenic mice. Despite being the same isotype, having similar affinity, opsonizing activity for phagocytosis, and in vivo half-life, the type II mAb tositumomab (B1) provided substantially longer depletion of B cells from the peripheral blood compared with the type I mAb rituximab (Rit m2a), and 1F5. This difference was also evident within the secondary lymphoid organs, in particular, the spleen. Failure to engage complement did not explain the efficacy of the type II reagents because type I mAbs mutated in the Fc domain (K322A) to prevent C1q binding still did not display equivalent efficacy. These results give support for the use of type II CD20 mAbs in human B-cell diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Complement activation impacts B-cell depletion by both type I and type II CD20 monoclonal antibodies Frank J. Beurskens, Sigrid R. Ruuls, Patrick J. Engelberts, Tom Vink, Wendy J. Mackus, Jan G. J. van de Winkel, and Paul W. H. I. Parren Blood 2008 112: 4354-4355. [Full Text] [PDF] Response: Superior B cell–depleting activity of type II anti-CD20 mAb is not due to activation of complement Stephen A. Beers, Mark S. Cragg, and Martin J. Glennie Blood 2008 112: 4355-4356. [Full Text] [PDF]

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